crossing96/oncoscreening huggingface dataset:
The Role of Radical Cystectomy with Orthotopic Neobladder Reconstruction in Patients Developing Bladder Cancer after Prior Radical Prostatectomy, Radiation Therapy, or BPH Surgery.	INTRODUCTION: Current evidence suggests that prior prostatic interventions, such as prostatectomy, radiation, or transurethral surgery, may increase the risk of incontinence in patients undergoing radical cystectomy (RC) with ileal orthotopic neobladder reconstruction. We aimed to evaluate the short- and long-term complications, functional outcomes of neobladder reconstruction in patients undergoing RC after prior prostatic procedures. METHODS: We analyzed patients who underwent RC after prior prostatic intervention in our department from 2013 to 2022. A comparison was made between patients receiving neobladder reconstruction (ONB) versus ileal conduit, including propensity score matching for age and preoperative continence. RESULTS: We included 79 patients who underwent RC for bladder cancer after prior prostatic intervention. Of them, 43 (54%) patients had previously undergone BPH surgery, 29 (37%) radical prostatectomy, and 7 (9%) prostate radiation therapy. An ileal conduit was performed in 62 (78%) cases. Patients presented similar baseline characteristics, perioperative complications, and quality of life after RC. Accordingly, after propensity-score-matching patients with ONB after prior prostatic intervention and patients who received ONB without prior prostatic intervention did not differ significantly in their baseline characteristics, perioperative complications, and quality of life. Overall, 24% of patients without prior intervention reported incontinence, compared to 53% with prior prostatic intervention. CONCLUSION: Neobladder reconstruction remains to be a feasible option in patients undergoing RC after prior prostatic intervention.	bladder
Understanding patient perspectives in the management of their muscle-invasive bladder cancer.	OBJECTIVES: To evaluate the impact of advocacy efforts by organisations such as the Bladder Cancer Advocacy Network (BCAN) to increase awareness about the signs, symptoms, diagnosis, treatment and need for a multidisciplinary approach to the care of patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We developed a 32-question survey with input from physicians, nurses, patients and caregivers. The survey was posted on the BCAN website between August 2013 and September 2014 (Cohort A) and again between June 2023 and April 2024 (Cohort B). Questions focused on time from initial symptoms to diagnosis and treatment, proportion seeing a medical oncologist or radiation oncologist, treatments offered/received, and patient satisfaction with their treatment choices. RESULTS: Overall, 337 self-selected patients mostly white males from the US or Canada, with at least an undergraduate education completed the survey. There were 243 patients in Cohort A and 94 patients in Cohort B. The median age (range) at diagnosis was 61 (31-93) in Cohort A and 63 (38-87) in Cohort B. The most common presenting symptom was hematuria. In Cohorts A and B, 35% vs 30% (P = 0.56) waited >3 months to seek medical attention, and in 38% vs 43% (P = 0.76) it took >3 months to obtain a diagnosis. Men were more likely than women to be diagnosed within 1-2 months in both cohorts (Cohort A: 68% vs 47%; P = 0.03, Cohort B: 70% vs 37%; P = 0.03). Preoperative consultation with a radiation oncologist and bladder-sparing use were infrequent. More patients in Cohort A (77%) felt they had enough time to make decisions compared to Cohort B (67%) (P = 0.004). Most patients were satisfied with their treatment choices. CONCLUSIONS: There are ongoing areas of unmet need in MIBC, including reducing time to definitive diagnosis and treatment, especially in women, and increasing multidisciplinary assessments prior to definitive surgery. Respondents were self-selected, had access to the BCAN website, and were highly educated, potentially limiting the generalizability of these results.	bladder
Efficacy of scheduled intravenous acetaminophen administration for catheter-related bladder discomfort in patients after transurethral resection of bladder tumors: A prospective randomized pilot study.	PURPOSE: Scheduled administration of intravenous acetaminophen improves catheter-related bladder discomfort (CRBD) after urological surgery. However its efficacy for patients undergoing transurethral resection of bladder tumors (TURBT) remains unclear. This study aimed to investigate the efficacy of scheduled administration of intravenous acetaminophen after TURBT. MATERIALS AND METHODS: At the end of surgery, patients in both the control (n=39) and the scheduled administration (n=45) groups received analgesics at the discretion of the anesthesiologists. In the scheduled administration group, intravenous acetaminophen was administered every 4 hours for 12 hours after the surgery. Both groups were administered on-demand analgesics as needed. The primary outcome was CRBD scores, and the secondary outcomes were the face rating scale for lower abdominal pain, administration rates of additional analgesics, durations of bladder catheterization, lengths of postoperative hospital stay, and postoperative complication rate. RESULTS: The scheduled administration group had significantly lower CRBD scores than those of the control group at 8 hours postoperatively (p=0.014), and lower administration rates of additional analgesics 4-8 hours (p=0.029) and 8-12 hours (p=0.027) postoperatively compared to those of the control group. Other secondary outcomes were not significantly different between the groups (all p>0.05). The scheduled administration group did not have postoperative complications related to the scheduled administration of intravenous acetaminophen. CONCLUSIONS: Scheduled intravenous acetaminophen administration alleviated postoperative CRBD and reduced the need for additional analgesics in patients who underwent TURBT. These findings can be utilized to improve the quality of postoperative care.	bladder
The effect of chronic kidney disease on adverse in-hospital outcomes after radical cystectomy with ileal conduit urinary diversion.	PURPOSE: Chronic kidney disease (CKD) is frequent in bladder cancer patients undergoing radical cystectomy (RC) with ileal conduit. However, the effect of CKD on adverse in-hospital outcomes after ileal conduit RC is not well known. METHODS: Descriptive analyses, propensity score matching (PSM), and multivariable logistic and Poisson regression models were used to address National Inpatient Sample patients treated with ileal conduit RC between 2006 and 2019. CKD severity was stratified as mild (stage II) vs. moderate (stage III) vs. severe (stage IV/V). RESULTS: Of 13,359 patients treated with RC with ileal conduit, 1973 (14.8%) had CKD. Of those, 956 (48.5%), 802 (40.6%), and 215 (10.9%) were classified as mild, moderate, or severe CKD, respectively. CKD rate increased from 4.1 to 21.9% (2006-2019, EAPC: +8.9%, p < 0.001). CKD RC patients exhibited higher rates of adverse in-hospital outcomes in 11 of 15 categories. The absolute differences were largest for overall complications (+ 13.2%), prolonged length of stay (+ 7.0%), blood transfusions (+ 6.0%, all p < 0.001). After detailed multivariable adjustment, CKD was an independent predictor of 11 of 15 adverse in-hospital outcomes' categories. The detrimental effect of CKD was most pronounced for dialysis (OR 7.09), overall complications (OR 1.84), and neurological complications (OR 1.61, all p < 0.001). Finally, a dose-response effect according to CKD severity on adverse in-hospital outcomes was observed in eight of 15 categories. CONCLUSIONS: CKD RC patients invariably exhibited higher rates of adverse in-hospital outcomes after RC with ileal conduit. In consequence this patient group should receive particularly strong consideration for preoperative optimization.	bladder
Analysis of Neoadjuvant Immunotherapy and Chemotherapy for Muscle-Invasive Bladder Cancer in a National Registry.	BACKGROUND: Based on remarkable success in the metastatic/locally advanced space, Neoadjuvant Immunotherapy (NIO) is a promising novel treatment option for Muscle-Invasive Bladder Cancer (MIBC). Here, we assess factors associated with NIO and describe survival outcomes following NIO use in MIBC patients. METHODS: The NCDB was used to identify 5,823 qualifying patients with a diagnosis of urothelial bladder cancer, T2-4N0-3M0 clinical stage and who received NIO or NAC prior to radical cystectomy between 2006 and 2019. NAC and NIO patient groups with similar clinical and demographic characteristics were defined using a 1:1 propensity score matching method. RESULTS: Mean age at diagnosis was significantly higher in NIO patients compared to NAC patients (70.22 ± 9.2 vs. 65.33 ± 9.1 years, P < .001). NAC administration correlated with an increased odds of pathologic complete response (pCR) compared to NIO in the unmatched (OR: 3.825, 95% CI: 1.972-7.417, P < .001) and matched (OR: 6.771, 95% CI: 2.624-17.473, P < .001) analyses. Finally, Cox proportional hazard model and Kaplan-Meier analysis revealed no difference in overall survival between NAC and NIO administration in the unmatched or matched analysis. CONCLUSION: In this study, older age, higher income and longer distance to facility were associated with the use of NIO compared to NAC. NIO administration was less effective at achieving pR and pCR compared to NAC. There was no observed difference in overall survival between patients that received NIO and those that received NAC. The ongoing phase III trials in this space should help to clarify the role of NIO.	bladder
[Value of whole-lesion apparent diffusion coefficient histogram parameters in preoperative differentiation of histological grade of bladder urothelial carcinoma].	Objective: To explore the clinical value of histogram parameters of the whole-leison apparent diffusion coefficient (ADC) in the histological grade of bladder urothelial carcinoma before operation. Methods: A retrospective analysis was conducted on patients with pathologically-proven bladder urothelial carcinoma who underwent preoperative bladder MRI at the First Medical Center of Chinese PLA General Hospital between January 1, 2019 and July 30, 2022. The patients were divided into high-grade and low-grade groups based on the histological grading of bladder urothelial carcinoma. The ADC histogram parameters of the two groups were compared. Multivariate logistic regression analyses were used to identify associated factors of high-grade bladder urothelial carcinoma. The diagnostic performance of the histogram parameters for the histological grade of bladder urothelial carcinoma was analyzed using receiver operating characteristic (ROC) curves. Results: A total of 63 patients were included, aged [M (Q(1), Q(3)), 64 (42, 84)] years and comprising 52 males (82.5%). Among them, 30 patients (47.6%) were classified into the low-grade group, and 33 patients (52.4%) into the high-grade group. Differences were observed between the two groups in tumor volume, ADC(mean), ADC(1%), ADC(5%), ADC(10%), ADC(25%), ADC(50%), ADC(75%), ADC(90%), ADC(95%), ADC(99%), variance, kurtosis and skewness (all P<0.05). ADC(mean) (OR=1.042, 95%CI: 1.004-1.082), ADC(10%) (OR=0.975, 95%CI: 0.950-0.999) and ADC(75%) (OR=0.979, 95%CI: 0.962-0.997) were associated with high-grade bladder urothelial carcinoma. The area under the curve (AUC) of ADC(mean), ADC(10%) and ADC(75%) for differentiating the histological grade of bladder urothelial carcinoma before surgery were 0.772 (95%CI: 0.649-0.868), 0.690 (95%CI: 0.561-0.800) and 0.816 (95%CI: 0.698-0.902), respectively. The combined model of these 3 parameters demonstrated an AUC of 0.853 (95%CI: 0.741-0.929), with a sensitivity of 78.8% and a specificity of 83.3%. The diagnostic performance of the combined model was superior to that of ADC(10%) alone (P=0.017), but no statistically significant differences were observed compared to ADC(mean) and ADC(75%) (both P>0.05). Conclusions: Whole-lesion ADC histogram parameters, including ADC(mean), ADC(10%), ADC(75%) and the combined model of these 3 parameters could be utilized for the histological grade of bladder urothelial carcinoma before operation, with high sensitivity and specificity.	bladder
Perioperative and Oncologic Outcomes of Robot-assisted Versus Laparoscopic Radical Cystectomy in Patients With Bladder Cancer.	BACKGROUND/AIM: Few studies have verified the relationship between treatment outcomes of robot-assisted radical cystectomy (RARC) and laparoscopic radical cystectomy (LRC). This study aimed to compare the perioperative and oncologic outcomes between RARC and LRC. PATIENTS AND METHODS: Medical records of 75 patients (45 RARC and 30 LRC) who underwent radical cystectomy and standard or higher lymph node dissection between April 2013 and December 2019 at the Tottori University and other satellite hospitals were reviewed. RESULTS: The operative time was shorter in the LRC group. Mean estimated blood loss was lower in the RARC group. No differences were noted in the complication rates. The mean number of lymph nodes removed was 23.1 in the RARC group and 13.9 in the LRC group (p<0.001). Cox proportional hazards regression analysis showed that the tumor variant of the transurethrally resected bladder tumor (TUR-BT) tissue (p=0.032) and lymph node metastasis (p= 0.041) were significantly associated with a higher risk of cancer-specific survival (CSS). No difference in the CSS (p= 0.337) and recurrence-free survival (p=0.448) was found in all patients having either RARC or LRC. However, the CSS of RARC was higher than that of LRC (p=0.032) in patients with locally advanced stages of bladder cancer such as pathological T stage ≥3 or pathological lymph node positivity. CONCLUSION: In patients with locally advanced bladder cancer pathological T stage ≥3 or pathological lymph node positivity, LRC appears to be associated with shorter CSS than RARC.	bladder
Nutraceutical Evaluation of Trigonelline's Therapeutic Potential by Targeting Bladder Cancer Stem Cells and Cancer-Associated Fibroblasts via Downregulation of TGFβ3/GLI2/YAP1 Signaling Hub.	Trigonelline (TGN), an alkaloid identified in medicinal plants such as coffee (Coffea spp.) and fenugreek (Trigonella foenum-graecum), has demonstrated significant anticancer properties across various malignancies, yet its efficacy in bladder cancer (BLCA) remains underappreciated. This study investigates TGN's role in modulating cancer stem cells (CSCs) and the tumor microenvironment (TME), two key contributors to BLCA progression and chemoresistance. Through comprehensive bioinformatics analyses of BLCA patient datasets, a TGY signature (TGFβ3, GLI2, YAP1) was identified as a critical signaling hub associated with poor prognosis, therapeutic resistance, and CSC generation. Computational docking studies revealed TGN's high binding affinity to the TGY signature, TGFβ3 (ΔG = -3.9 kcal/mol), GLI2 (ΔG = -4.2 kcal/mol), YAP1 (ΔG = -3.4 kcal/mol), suggesting its potential to disrupt this signaling axis. In vitro experiments demonstrated that TGN effectively inhibited BLCA cell proliferation, colony formation, and tumorspheroid growth while significantly enhancing cisplatin sensitivity in resistant cell lines. Notably, TGN reduced the transformation of fibroblasts into cancer-associated fibroblasts (CAFs) through the downregulation of α-SMA and FAP (Fibroblast activation protein) expression, indicating its capacity to normalize the TME. Real-time PCR analysis revealed that TGN treatment significantly reduced markers of epithelial-mesenchymal transition and stemness pathways. Our preclinical mouse study demonstrated that combining TGN and cisplatin significantly reduced tumorigenesis in cisplatin-resistant bladder tumoroids harboring CAFs. Importantly, this combination therapy showed no apparent systematic toxicity, suggesting a favorable safety profile. Our findings reveal novel molecular targets of TGN in bladder cancer; TGN acts as a potent disruptor of the TGY signaling axis and a normalizer of the TME by reducing CAF transformation. In sum, our findings advocate for TGN's further exploration as a candidate for combination therapy in drug-resistant BLCA, with the potential to improve patient outcomes by simultaneously targeting both CSCs and the TME, serving as a foundation for future clinical trials.	bladder
In vitro Evaluation of Zinc Oxide-Metformin Folic Acid Nanocomposite as a Targeted Drug Delivery System for Cancer Therapy.	BACKGROUND: Cancer has become the second cause of death worldwide after cardiovascular diseases. Thus, the development of efficient therapeutic approaches for cancer treatment seems necessary. One of the promising approaches is depending on nanotechnology in terms of drug delivery systems. ZnO nanoparticles have been approved for their efficiency as a drug delivery system due to their unique properties. Metformin (1, 1-dimethylbiguanide hydrochloride) is widely used as an anti-diabetic drug. However, recent studies have explored its repurposing as an anti-cancer drug. OBJECTIVE: The present study aims to evaluate the feasibility and efficiency of a folic acid-metformin ZnO nanoparticle delivery system in the treatment of melanoma and bladder cancer cell lines. METHODS: ZnO nanoparticles were chemically synthesized, loaded with metformin, and conjugated with folic acid at concentrations of 3% and 5%. Characterization of the nanoparticles was conducted using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential analysis, and transmission electron microscopy (TEM). The cytotoxicity of ZnO nanoparticles was evaluated against human melanoma (A375) and bladder cancer (T24) cell lines via the MTT assay, with the determination of the half-maximal inhibitory concentration (IC50). RESULTS: ZnO nanoparticles were successfully synthesized with a spherical shape, size < 20 nm, and high homogeneity. Encapsulation efficiency of metformin on ZnO nanoparticles ranged from 95% to 98%. The folic acid-metformin ZnO nanoparticles demonstrated significant cytotoxic effects against both A375 and T24 cell lines in a dose-dependent manner. The IC50 values revealed higher sensitivity of T24 bladder cancer cells compared to A375 melanoma cells. CONCLUSION: Overall, our study highlights the promise of the ZnO-metformin-folic acid nanoparticles as an efficient drug delivery system for cancer treatment. These results open up a potentially valuable line of novel therapeutic applications.	bladder
Genomic features of bladder neuroendocrine carcinoma with composite histology.	Neuroendocrine carcinoma (NEC) is a rare and aggressive malignancy derived from multiple body parts, with the urogenital organs being the second-largest extrapulmonary sites. The detailed mechanism of bladder NEC pathogenesis remains unknown. We reviewed data from 23 patients diagnosed with NEC from urogenital organs (bladder and prostate) and conducted targeted sequencing of 523 cancer-related genes, focusing on bladder NEC. While 14 cases featured a pure NEC histology, the remaining nine cases included NEC histology mixed with other tumors, such as urothelial carcinoma (UC) or adenocarcinoma. Median overall survival in the entire cohort was 11.1 months, and survival curves were comparable between pure NEC and NEC of mixed appearance. Major mutations detected in the NEC component were in TP53 (38%), TERT promoter (31%), PIK3CA (25%), histone-modification genes (19%), and RB1 (19%). The BARD1 frameshift variant related to homologous recombination was also detected in one patient. More than half of the patients had a high total mutational burden (TMB; ≥10), including two with a TMB ≥45. Intriguingly, at least one identical gene variant in driver genes was detected between NEC and non-NEC (UC) components in the four bladder specimens analyzed. These results highlight the possibility of shared genetic background between bladder NEC and UC. Additionally, several cases harbored druggable gene alterations as presented by TMB-high. Our presentation of the histopathological and molecular features of NEC may help clarify the underlying mechanisms and contribute to efficient treatment of the disease.	bladder
DGKα Enhances Tumorigenic Activity in Bladder Cancer Patients With Chronic Kidney Disease.	INTRODUCTION: Chronic kidney disease (CKD) is a risk factor for bladder cancer (BC) and is reportedly involved in its recurrence and progression. This study aimed to determine the molecular mechanisms underlying the development of BC in patients with CKD. METHODS: First, we generated the CKD mouse model according to a unilateral two-stage renal ischemia-reperfusion injury protocol using wild-type C57BL/6 mice. Second, we conducted a molecular functional analysis of DGKα in BC and investigated the contribution of DGKα to cell invasion, migration, and proliferation activity using human BC cell lines. RESULTS: After confirming elevated serum creatinine levels in mice, the bladder was dissected, and mRNA sequencing of bladder urothelial cells was conducted. Gene expression profiling revealed remarkable upregulation in diacylglycerol kinase alpha (DGKα) level compared to that in control urothelial cells. DGKα-knockdown cells displayed significantly decreased invasion, migration, and proliferation activity compared to the controls. Next, we conducted a clinical analysis of DGKα in BC patients and performed immunohistochemistry (IHC) on samples from patients treated with radical cystectomy. IHC staining revealed that DGKα-positive cases had significantly worse recurrence-free and cancer-specific survival rates (p = 0.036 and = 0.003, respectively). CONCLUSION: DGKα expression is associated with tumorigenic activity in BC. Therefore, it is speculated that increased expression of DGKα in CKD cases is involved in the malignant potentials in BC. In conclusion, the crucial role of DGKα in BC is suggested, and it may be one of the factors contributing to poor prognosis in BC patients with CKD.	bladder
Unlocking the mechanisms underlying the activity of pembrolizumab plus enfortumab vedotin in patients with urothelial carcinoma.	INTRODUCTION: Urothelial carcinoma (UC) is frequently associated with a poor prognosis in patients with advanced disease. A strong biological rationale supports the investigation of combining antibody-drug conjugates (ADCs) with immunotherapy to overcome the occurrence of resistance and improve patient outcomes. AREAS COVERED: In this review, we illustrate the mechanisms of action of pembrolizumab and enfortumab vedotin (EV) and the immune and biological rationales underlying their synergy in mUC patients. EXPERT OPINION: The results of the combination of EV and pembrolizumab represent a ray of light in the therapeutic scenario of mUC patients. A deeper understanding of the mechanisms underlying the synergistic effects of these agents will be crucial to reduce drug-resistance and further improve the outcome of mUC patients.	bladder